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4dk9

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==Crystal Structure of MBD4 Catalytic Domain Bound to Abasic DNA==
==Crystal Structure of MBD4 Catalytic Domain Bound to Abasic DNA==
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<StructureSection load='4dk9' size='340' side='right' caption='[[4dk9]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
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<StructureSection load='4dk9' size='340' side='right'caption='[[4dk9]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4dk9]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DK9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DK9 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4dk9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DK9 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.76&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MBD4, MED1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dk9 OCA], [https://pdbe.org/4dk9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dk9 RCSB], [https://www.ebi.ac.uk/pdbsum/4dk9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dk9 ProSAT]</span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dk9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dk9 RCSB], [http://www.ebi.ac.uk/pdbsum/4dk9 PDBsum]</span></td></tr>
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</table>
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<table>
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== Function ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/MBD4_HUMAN MBD4_HUMAN] Mismatch-specific DNA N-glycosylase involved in DNA repair. Has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites. Can also remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase activity. Was first identified as methyl-CpG-binding protein.<ref>PMID:10097147</ref> <ref>PMID:10930409</ref>
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== Publication Abstract from PubMed ==
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The mammalian repair protein MBD4 (methyl-CpG-binding domain IV) excises thymine from mutagenic G.T mispairs generated by deamination of 5-methylcytosine (mC), and downstream base excision repair proteins restore a G.C pair. MBD4 is also implicated in active DNA demethylation by initiating base excision repair of G.T mispairs generated by a deaminase enzyme. The question of how mismatch glycosylases attain specificity for excising thymine from G.T, but not A.T, pairs remains largely unresolved. Here, we report a crystal structure of the glycosylase domain of human MBD4 (residues 427-580) bound to DNA containing an abasic nucleotide paired with guanine, providing a glimpse of the enzyme-product complex. The mismatched guanine remains intrahelical, nestled into a recognition pocket. MBD4 provides selective interactions with the mismatched guanine (N1H, N2H(2)) that are not compatible with adenine, which likely confer mismatch specificity. The structure reveals no interactions that would be expected to provide the MBD4 glycosylase domain with specificity for acting at CpG sites. Accordingly, we find modest 1.5- to 2.7-fold reductions in G.T activity upon altering the CpG context. In contrast, 37- to 580-fold effects were observed previously for thymine DNA glycosylase. These findings suggest that specificity of MBD4 for acting at CpG sites depends largely on its methyl-CpG-binding domain, which binds preferably to G.T mispairs in a methylated CpG site. MBD4 glycosylase cannot excise 5-formylcytosine (fC) or 5-carboxylcytosine (caC), intermediates in a Tet (ten eleven translocation)-initiated DNA demethylation pathway. Our structure suggests that MBD4 does not provide the electrostatic interactions needed to excise these oxidized forms of mC.
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Crystal Structure of Human Methyl-Binding Domain IV Glycosylase Bound to Abasic DNA.,Manvilla BA, Maiti A, Begley MC, Toth EA, Drohat AC J Mol Biol. 2012 May 2. PMID:22560993<ref>PMID:22560993</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Methyl CpG binding protein 3D structures|Methyl CpG binding protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Drohat, A C.]]
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[[Category: Large Structures]]
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[[Category: Manvilla, B A.]]
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[[Category: Drohat AC]]
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[[Category: Toth, E A.]]
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[[Category: Manvilla BA]]
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[[Category: Hydrolase-dna complex]]
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[[Category: Toth EA]]
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[[Category: Protein-dna complex]]
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Current revision

Crystal Structure of MBD4 Catalytic Domain Bound to Abasic DNA

PDB ID 4dk9

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